The objective of this project is to continue studies on the effect of tissue culture of adult isolated islets in conjuction with pretreatment of donor animals for the removal of passenger lymphocytes and macrophages from the islets prior to transplantation in order to obtain prolongation of survival of allografts of islets. Inbred strains of rats will be used for donors and recipients using strains with weak histocompatibility differences and strong histocompatibility barriers. The inbred Lewis strain of rat will be used as recipients and diabetes is produced by streptozotocin. Islets are isolated from the donor animals by the collagenase technique and transplanted via the portal vein. The isolated islets are cultured in the presence of anti-lymphocyte serum and complement to remove lymphocytes prior to transplantation. The donors are treated with either silica or total body irradiation prior to isolation of the islets. Cyclophosphamide may also be used to pretreat the donor animals. Studies will also be accomplished to produce an anti-macrophage serum for the in vitro removal of macrophages from isolated islets maintained in culture prior to transplantation. Studies on the effect of silica added to cultures of islets will be determined with the hope of removing macrophages. The raft method for flotation culture will be used to determine whether isolated islets can be maintained in culture by this technique. If this is successful, this technique will be used for long-term maintenance of the islets to remove passenger macrophages and lymphocytes prior to transplantation. After these studies on allotransplants of islets are completed similar studies will be accomplished with xenografts of islets using the information gained from the allograft studies.